Mean SDs Research Articles

Investigation of number of replicate measurements required to meet cigarette smoke chemistry regulatory requirements measured under Canadian intense smoking conditions

There has been increased interest in recent years in regulatory reporting of cigarette smoke toxicants. There is a great deal of diversity in current regulatory standards around the world in terms of the identities of regulated toxicants, and the number of replicate analyses stipulated for their measurement. Furthermore, analytical methods developed collaboratively by several organisations and intended for regulatory analysis generally differ in their recommended replicate numbers to those stipulated by regulators. In view of these inconsistencies, we undertook an exercise to examine the most appropriate numbers of replicates required for regulatory analysis of cigarette smoke toxicants.A one-point-in-time sampling exercise was undertaken of the German cigarette market, with 161 brands sampled and analysed in a single laboratory using Canadian Intense smoking conditions. Seven replicate measurements were made for each analyte and product, other than nicotine, CO and nicotine-free dry particulate matter for which eight replicate measurements were made. After confirming the absence of order of analysis effects, a variety of statistical tests (such as group assessment, paired comparisons, linear regression models and ratio analysis) were conducted examining mean values, SDs and CVs to identify the role of numbers of analytical replicates on data quality.The statistical analysis showed no difference in mean values for any of the 18 toxicants irrespective of replicate numbers (between 3 and 7 or 8). The large majority of analytes showed no difference in data variability with replicate number; but some very small differences (much lower than within product variability) were observed for a minority of compounds. Similarly, paired analysis showed no significant differences between mean values obtained using different replicate numbers in most cases, apart from very low differences (<5%) for a small number. Linear regression analysis showed correlations around 96 to 98% (other than crotonaldehyde at 91%) between values obtained with 3 vs 7 replicates. Similarly, per product mean value ratio analysis showed 95% consistency between values obtained with 3 and 7 replicates.We therefore conclude that three replicates is sufficient for precise determination of cigarette mainstream smoke toxicant emissions, and that use of 7 replicates as stipulated in some regulator jurisdictions does not offer any greater accuracy or precision.

SUN-250 Natural History of Growth in Patients with SHOX Gene Haploinsufficiency and Impact of Treatment with rhGH in Adult Height

Introduction: The SHOX gene haploinsufficiency is the main monogenic cause of short stature, being observed in 56% to 100% of patients with Leri-Weill dyschondrosthosis (LWD) and in 1% to 14% of children with idiopathic short stature (ISS). The diagnosis allows the establishment of a suitable prognosis for adult height, indication of rhGH treatment and genetic counseling. Objectives: To describe a cohort of 45 children (24 female) with molecular diagnosis of heterozygous SHOX defects, focusing on achievement of adult height. Materials and Methods: We analyzed retrospective data from 37 families in that defects in the SHOX gene were identified. The molecular study was performed by MLPA followed by gene sequencing. Results: In 64% of the families there was deletions in SHOX gene, 20% deletions in SHOX expression regulatory region and 16% point mutations. Among the 45 patients diagnosed during childhood, 14 were identified by family screening and 31 were index case. The mean age at diagnosis was 10.2 ± 3.2y, BMI SDS = 0.9 ± 0.8, height SDS of affected parent -2.4 ± 1.1 and height SDS of non-affected parent was -1.1 ± 1.2. The index cases were shorter than the children diagnosed by screening (Height SDS of -2.2 ± 1.0 vs. -1.5 ± 0.7, respectively; p 0.038). The majority (80%) of these children had disproportionate short stature (Sitting height by total height SDS = 3.5 ± 1.7), and 47% had Madelung deformity. Twenty-six patients reached adult height, 16 of them were treated with rhGH (mean duration of treatment = 4.8 ± 3.0 y, mean dose: 50 µg/kg/d). Eight patients (3 boys and 5 girls) were also treated with GnRH analog due to a low predicted adult height (mean duration of GnRHa was 3.1 ± 1.7y). At the first evaluation, treated patients were shorter than untreated ones (Height SDS = -2.3 ± 1.1 vs. -1.5 ± 0.6, respectively; p = 0.059). Mean adult height SDS was similar between treated and non-treated patients (height SDS -2.0 ± 1.2 vs. -2.6 ± 0.7, respectively, p = 0.179). Treated patients showed a slighted improvement of height SDS from the start the therapy to adult height (∆Height SDS = 0.3 ± 0.7), while untreated patients had loss of height SDS (∆Height SDS -1.2 ± 0.7 p <0.001). Of the treated patients 63% reached normal height (Height SDS >-2) whereas 75% of untreated patients had short stature at adult height (Z <-2). Conclusion: Treatment with rhGH promotes stature gain in patients with SHOX haploinsufficiency. Genetic screening in children with short stature allows the identification of new carriers of SHOX defect and precocious rhGH therapy can avoid the lost of 1 SDS of height between childhood and adult life.

SAT-LB051 Longitudinal Growth in Height and Changes in Body Proportions in Children with Hereditary Hypophosphatemic Rickets in a Single Center

Children with Hereditary Hyphophosphatemic Rickets (HHR) are characterized by hypophosphatemia, rickets and disproportionate short stature. Aim: To analyze growth pattern in height (H) and body proportions during childhood and puberty in a cohort of 96 children, 29 males (M), 67 females (F), with HHR treated with standard dosis of phosphorus and calcitriol followed in a single center. Methods: Body proportions were evaluated by sitting height/height (SH/H) ratio. Patients were divided in 2 groups (G) according to their compliance to treatment: good (G1) and poor (G2). Pubertal growth was evaluated by Preece Baines model 1in 19 patients (8 M, 11 F), while adult H was achieved in 42 patients (13 M, 29 F). Molecular characterization of PHEX gene was performed by automated sequencing analysis in 27 cases (8 familiar, 15 sporadic). Results: Birth weights and lengths were no different from national reference data in both sexes. At first appointment, median (range) age (years): 3.5 (0.2/14.6); H SDS: -2.3 (0.6/-5.88) and SH/H ratio SDS: 3.4 (-1.7/10.4). Mean growth velocity SDS (+/-SD) at take off was significantly higher in G1: -0.7 (0.6) than in G2: -2.6 (0.8) (p<0.00001). During puberty, mean growth velocity SDS (+/-SD) at peak was significantly higher in G1: -0.48 (1.38) than in G2: -2.73 (1.3) (p<0.002). Median (range) adult H SDS was significantly higher in M G1: -2.1 (-2.9/-1.8) and F G1: -2.4 (-3/-0.9) than in M G2: -4.7 (-6.9/-0.7) and F G2: -4.1 (-6.6/-2.7) (p<0.005). A tendency to higher mean total growth gain during puberty (cm) in G1 vs G2 in both sexes was found (p=0.1). Median (range) adult SH/H ratio SDS was significantly lower in G1: 2.32 (0.5/5.3) than in G2: 6.21 (2.5/8.1) (p=0.0016). PHEX gene deleterious variants were found in 87% of familiar and in 53% of sporadic cases and 6 novel mutations (p.Lys468Asn, c.2070+5G>A, Ex2 deletion, p.Gln666Ter, p.Gln682IlefsTer36, p.Met98SerfsTer10) were pathogenic by in silico tools. Conclusions: Patients with HHR were born with adequate length for gestational age. Short stature and body disproportion was already found at diagnosis. During childhood and puberty, growth retardation and body disproportions were maintained in G1 while were aggravated in G2. Consequently, adult H and body proportions were significantly better in G1. Early and appropriate diagnosis and treatment improve adult H and body proportions prognosis. Frequency of PHEX mutations was similar to other cohorts reported. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency.

Context Abnormalities in the hypothalamo-pituitary-gonadal axis have long been reported in Noonan syndrome (NS) males with only few data available in prepubertal children. Objective The aim of this study was to describe the gonadal function of NS males from childhood to adulthood. Design It is a retrospective chart review. Patients and methods A total of 37 males with a genetically confirmed diagnosis of NS were included. Clinical and genetic features, as well as serum hormone levels (LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B) were analysed. Results Of the 37 patients, 16 (43%) children had entered puberty at a median age of 13.5 years (range: 11.4-15.0 years); age at pubertal onset was negatively correlated with BMI SDS (r = -0.541; P = 0.022). In pubertal boys, testosterone levels were normal suggesting a normal Leydig cell function. In contrast, NS patients had significant lower levels of AMH (mean SDS: -0.6 ± 1.1; P = 0.003) and inhibin B (mean SDS: -1.1 ± 1.2; P < 0.001) compared with the general population, suggesting a Sertoli cell dysfunction. Lower AMH and inhibin B levels were found in NS-PTPN11 patients, whereas these markers did not differ from healthy children in SOS1 patients. No difference was found between cryptorchid and non-cryptorchid patients for AMH and inhibin B levels (P = 0.43 and 0.62 respectively). Four NS-PTPN11 patients had a severe primary hypogonadism with azoospermia/cryptozoospermia. Conclusions NS males display Sertoli cell-specific primary testicular insufficiency, whereas Leydig cell function seems to be unaffected.

Integrated analysis of long-term growth and bone development in pediatric and adolescent patients receiving bevacizumab.

We conducted an integrated analysis of clinical data to describe long-term effects of bevacizumab on growth and bone development in pediatric and adolescent patients with solid tumors. Clinical data were pooled from five phase I/II trials of bevacizumab versus chemotherapy: BERNIE, HERBY, and AVF4117s enrolled newly diagnosed patients, AVF3842s and AVF2771s enrolled patients with relapsed/refractory disease. Height, weight, body mass index (BMI), and bone-age data were pooled by treatment group. Growth charts were used to track and monitor growth in relation to a reference population of healthy children. Bone age was measured based on X-ray of the left hand and wrist. Analyses were exploratory/descriptive. Overall, 268 patients received bevacizumab ± chemotherapy and 135 received chemotherapy alone. Baseline characteristics were generally balanced. Median duration of long-term follow-up was 41.8 months (range, 2.4-75.1) with bevacizumab and 22.9 months (range, 2.8-69.2) with chemotherapy alone. Patients had age-appropriate baseline height and weight. Mean height and weight percentiles decreased over time in both treatment groups, but remained within the normal range (height: mean standard deviation score [SDS] range -2 to +3; weight: mean SDS range -2 to +1). Similar trends were seen in BMI. A tendency for reduced growth velocity relative to the reference population was observed at 6 months and 1year in both groups, but there was no additional decrease for patients receiving bevacizumab. Bevacizumab did not appear to have additional negative effects on growth or development of pediatric and adolescent patients with solid tumors.

Safety and effectiveness of escitalopram in an 8-week open study in Chinese patients with depression and anxiety.

BackgroundAnxiety symptoms usually worsen depression and functional impairment. The present study was aimed to evaluate the impact of escitalopram on social function and quality of life in major depressive disorder (MDD) patients with anxiety symptoms.Patients and methodsAdult MDD patients with functional impairment (Sheehan Disability Scale [SDS] score ≥9) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] score ≥14) received escitalopram (10–20 mg/day) for 8 weeks. Symptom status was assessed by SDS, Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A, and Quick Inventory of Depressive Symptomatology-Self Report scales. Safety was evaluated by treatment-emergent adverse events (TEAEs).ResultsOverall, 208 (79.7%) of 261 enrolled patients completed the 8-week treatment. Mean (SD) SDS and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form total scores were 17.4 (5.87) and 39.3 (14.43) at baseline, which improved to 7.6 (6.71) and 61.6 (15.80), respectively, at week 8. Totally, 59.2% of patients achieved functional remission (SDS≤6) and 61.7% of patients achieved depression remission (MADRS≤10) at week 8; 48.1% of patients achieved both functional and depression remission (SDS≤6 and MADRS≤10). The change in SDS total score was positively correlated with the change in MADRS and HAM-A total scores at each visit. Patient’s baseline SDS score was related with depression score (regression coefficient=0.40582, p=0.0005); remission of SDS was statistically related to a reduction of week 2 and week 6 HAM-A score (p<0.0001) and reduction of MADRS score (p<0.0001). Overall, 25.7% of patients reported ≥1 TEAEs. Most frequently reported TEAEs were nausea (5.8%), diarrhea (2.3%), and dizziness (2.7%). Most TEAEs were mild to moderate in severity. Four patients reported serious TEAEs, two patients reported suicide attempts, and one patient completed suicide.ConclusionEscitalopram (10–20 mg/day) treatment was efficacious in reducing depression, improving social function, and quality of life in MDD patients with anxiety symptoms. No new safety signals were identified.

Ultrasound Nomograms of the Fetal Optic Nerve Sheath Diameter.

Objective To construct prenatal age-specific reference intervals for sonographic measurements of the optic nerve sheath diameter (ONSD) during gestation in normal fetuses. Materials and Methods Prospective cross-sectional study of fetuses assessed in antenatal ultrasound units between 2010 and 2014. The examination was based on a technique for the sonographic assessment of ONSD previously published by our group. The mean values and SDs of the ONSD were modeled as a function of the gestational week by curve estimation analysis based on the highest adjusted R2 coefficient. Repeatability tests were performed to assess intraobserver variability and interobserver agreement. Results During the study period 364 healthy fetuses were enrolled. The mean values for the ONSD varied from 0.6 mm at 15–16 weeks to 2.8 mm at 37–38 weeks. The ONSD grows in a linear fashion throughout gestation, with a quadratic equation providing an optimal fit to the data (adjusted R2 = 0.957). Conclusion Sonographic age-specific references for the fetal ONSD are presented. This data may assist in the decision-making process in fetuses with a suspected increase in intracranial pressure, or anomalies affecting the development of optic stalks, such as optic hypoplasia and septo-optic dysplasia.

Ultrasound Nomograms of the Fetal Optic Nerve Sheath Diameter.

To construct prenatal age-specific reference intervals for sonographic measurements of the optic nerve sheath diameter (ONSD) during gestation in normal fetuses. Prospective cross-sectional study of fetuses assessed in antenatal ultrasound units between 2010 and 2014. The examination was based on a technique for the sonographic assessment of ONSD previously published by our group. The mean values and SDs of the ONSD were modeled as a function of the gestational week by curve estimation analysis based on the highest adjusted R2 coefficient. Repeatability tests were performed to assess intraobserver variability and interobserver agreement. During the study period 364 healthy fetuses were enrolled. The mean values for the ONSD varied from 0.6 mm at 15-16 weeks to 2.8 mm at 37-38 weeks. The ONSD grows in a linear fashion throughout gestation, with a quadratic equation providing an optimal fit to the data (adjusted R2 = 0.957). Sonographic age-specific references for the fetal ONSD are presented. This data may assist in the decision-making process in fetuses with a suspected increase in intracranial pressure, or anomalies affecting the development of optic stalks, such as optic hypoplasia and septo-optic dysplasia.

Can Patients With COPD Assimilate Disease-Specific Information During an Acute Exacerbation?: Results of a Pilot Randomized Controlled Trial

The study aimed to determine the feasibility and effectiveness of an introductory disease-specific educational program delivered during an acute exacerbation of COPD (AECOPD) on objective measures of disease-specific knowledge. Patients admitted to a community hospital with an AECOPD were randomly assigned to a control group (standard care) or intervention group (standard care+ brief education). The intervention group received two 30-min education sessions in hospital or at home within 2weeks of hospital admission. Feasibility measures included the number of eligible patients, compliance with the sessions, and number of follow-up measures completed. Disease-specific knowledge and informational needs were measured using the Bristol COPD Knowledge Questionnaire (BCKQ) and the Lung Information Needs Questionnaire (LINQ), respectively, before and after the intervention period. Thirty-one patients (mean age, 72 ± 10 years) with an AECOPD participated in the study. Of 102 approached patients, 75 consented to screening (73.5%) and 67 (66%) were eligible for the study. Thirty-four patients declined participation. All intervention patients (n= 15) completed the educational sessions and follow-up measures. Three patients (control group) did not complete the follow-up measures. The mean changes and SDs for the BCKQ in the intervention and control groups were 8 ± 5.14 and 3.4 ± 4.9, respectively (P= .02). No difference between groups was found for the LINQ (P= .80). A brief educational program delivered at the time of hospitalization for an AECOPD was feasible for a subset of patients, resulted in improved disease-specific knowledge, and may be a bridge to more active approaches. ClinicalTrials.gov; No.: NCT02321215; URL: www.clinicaltrials.gov.

Growth hormone-Insulin-like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune-Albright Syndrome.

In fibrous dysplasia (BFD), normal bone and bone marrow are replaced by fibro-osseous tissue, leading to fracture, deformity and pain. BFD may be isolated, or in association with cutaneous hyperpigmentation and/or hyperfunctioning endocrinopathies, termed McCune-Albright syndrome (MAS). GH hypersecretion has been described in 10%-20% of MAS-BFD patients. Aim of the study was to determine the impact of GH-insulin like growth factor 1 (IGF1) axis hyperactivity on MAS-BFD morbidities and the efficacy of GH excess therapy. A multicentric cross-sectional analysis was conducted on three different MAS cohorts. From 195 MAS patients, 37 subjects (19%) with GH excess were identified and compared with 34 MAS controls without GH hypersecretion. Mean head circumference SDS was significantly higher in GH excess: 4.025 SDS vs 0.683 SDS (P<.0001). The risk of optic neuropathy (Odds ratio 4.231; P=.039), hearing deficit (Odds ratio 2.961; P=.0481), facial asymmetry (Odds ratio 6.563; P=.0192), malignancies (Odds ratio 15.24; P=.0173) were higher in GH excess group. Overall, pharmacotherapy (octreotide alone 10-30mg/mo or with pegvisomant 10-20mg/d) was effective in IGF1 normalization (IGF1 Z-score between -2 and +2 SDS) in 21/29 patients (72.4%) with good compliance to the regimen. Late diagnosis and GH excess treatment after 16years old of age was associated with an increased risk of optic neuropathy (Odds ratio 4.500; P=.0491) and growth of pituitary adenomas (Odds ratio 7.846; P=.050). GH-IGF1 hyperactivity increases risk of morbidities in MAS. Medical therapy is effective in normalizing IGF1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH-secreting adenomas growth.

Assessment of Interprofessional Team Collaboration Scale (AITCS): Further Testing and Instrument Revision.

The need to be able to assess collaborative practice in health care teams has been recognized in response to the direction for team-based care in a number of policy documents. The purpose of this study is to report on further refinement of such a measurement instrument, the Assessment of Interprofessional Team Collaboration Scale (AITCS) first published in 2012. To support this refinement, two objectives were set: Objective 1: to determine whether the items from the data collected in 2016 load on the same factors as found for the 2012 version of the 37-item AITCS. Objective 2: to determine whether the items in the subscales of the AITCS could be reduced while retaining psychometric properties similar to those from the earlier versions of the AITCS. Initially, the overall data sets of 1002 respondents from two hospitals and four community agencies were analyzed for demographics and scale and subscale mean values, SDs, and mean item scores. After deletion of respondents because of missing data, 967 respondents were available for the first analysis. An exploratory factor analysis was then conducted to determine the factor structure. All respondents with any random missing data were further removed to reduce the data set to 676 responses, followed by a confirmatory factor analysis to find a model fit resulting in an item reduction in the scale. The result was a 23-item AITCS-II for practitioners that retained acceptable levels of reliability and validity within 3 subscales-partnership (8 items), cooperation (8 items), and coordination (7 items). The shortened version of the AITCS-II is a valid and reliable instrument that can be used to assess collaboration in health care teams in practice settings.

Single CT for attenuation correction of rest/stress cardiac SPECT perfusion imaging

Common practice is to use separate CT scans acquired during rest and stress for attenuation correction of SPECT myocardial perfusion imaging (MPI). We evaluated using a single CT scan to correct both rest and stress SPECT scans. Studies from 154 patients were reprocessed using one CT acquired at stress to correct both rest and stress scans (1CT) and compared to correction of each scan with its own CT (2CT). Two expert readers independently read the images and determined summed stress (SSS), rest (SRS), and difference (SDS) scores. The correlation in SRS between 2CT and 1CT was r ≥ 0.88. The concordance in SDS was ≥0.84 (kappa ≥ 0.62). The mean SDS difference between 2CT and 1CT for the averaged observer was not significantly different from zero (p > 0.31). 1CT images had a small but significant increase in SRS and an increase in SDS variability. However, the mean SDS difference was similar to the mean inter-observer SDS difference for the 2CT approach (−0.08 vs −0.23, p = 0.46) and had less uncertainty (1.02 vs 2.05, p < 0.001). Thus, the differences between 1CT and 2CT are unlikely to be clinically significant, and the 1CT approach is feasible for SPECT MPI.

We Matter Too! Addressing the Wellness of Program Coordinators in Graduate Medical Education.

Burnout and stress in medical settings have been associated with despondent staff and decreased productivity. Although Program Coordinators (PCs) play an integral role in residency training programs, there exist few, if any, interventions aimed at addressing their burnout. A longitudinal study design was used to evaluate data from residency/fellowship training PCs who participated in a wellness retreat held at a single institution in August 2016. Subjects completed anonymous, pre- and post-retreat questionnaires in addition to a 3-month follow-up questionnaire, which included questions used to assess aspects of job demand, resiliency, and well-being. The seven-item Physician Well-Being Index and a logistic regression model were used to assess well-being. Mean values and SDs were reported to examine changes in mental health scores and participants' job satisfaction over the course of the intervention. Nineteen of the 45 (43%) invited residency/fellowship training PCs completed data collection. Coordinators ranged in age from 25 to 64 years; all were female. Well-being, sleep, resiliency, and employee satisfaction scores improved over the assessment period. Well-being scores initially decreased by 0.37 at the postassessment, but increased at follow-up (mean: 2.0; SD 1.7). Stress scores increased from baseline to post, but decreased from baseline to follow-up: 0.2 and -0.2, respectively. Residency PCs experienced improvements in mental quality of life, resiliency, stress, and sleep scores on attending the wellness program. Attention to such findings may have important implications, as we address the burnout crisis in the medical education community.

Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction.

The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R1 and R2), and proton density were measured by automated software. The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R1, R2, and proton density showed slopes of -0.198 (P < .001), 0.156 (P = .04), and 0.488 (P < .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. Correlations between volume and R1, R2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.

Osteoporosis in patients with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare metabolic disease with painful photosensitivity due to protoporphyrin IX accumulation. To evaluate bone mineral density (BMD) and known osteoporosis risk factors in patients with EPP. Patients with EPP attending the Erasmus MC outpatient clinic who had undergone BMD measurements were included. Plasma 25 hydroxy (OH) vitamin D, alkaline phosphatase, parathyroid hormone and total protoporphyrin IX levels were measured; information on lifestyle, sunlight exposure and a bone-relevant physical exercise index [Bone Physical Activity Questionnaire (BPAQ) score] was obtained via questionnaires. BMD scores and the prevalence of osteopenia and osteoporosis in the EPP population were compared with a reference population. Forty-four patients with EPP (23 female, 21 male; mean age 37·6 years) were included. The mean SDs of the T-scores were -1·12 for the lumbar spine and -0·82 for the femoral neck (both P < 0·001). Osteopenia was present in 36%; osteoporosis in 23%. Based on the reference population the expected prevalence was 15% and 1%, respectively. Prevalence of vitamin D deficiency was 50% (defined as a 25-OH vitamin D level < 50 nmol L-1 ). Mean self-reported BPAQ score was 19·4 units (reference interval 19-24). Multiple linear regression analysis showed a significant influence of vitamin D deficiency and bone-relevant physical exercise score on BMD in patients with EPP. The prevalence of osteoporosis and osteopenia is greatly increased in patients with EPP. Alkaline phosphatase (related to vitamin D deficiency) and amount of weight-bearing exercise are significantly correlated with low BMD in this population.

Growth hormone treatment improves final height and nutritional status of children with chronic kidney disease and growth deceleration.

Growth retardation is a common complication of chronic kidney disease (CKD) in children. Treatment with recombinant human growth hormone (rhGH) has been used to help short children with CKD to attain a height more in keeping with their age group, but the scientific evidence regarding the effect of rhGH on final height is scarce. Final heights of children with CKD receiving rhGH treatment (cases) were compared with final heights of a matched cohort of children with CKD that did not receive rhGH therapy (controls). Sixty-eight rhGH-treated cases (44 boys) were compared with 92 untreated controls (60 boys). Mean duration of rhGH therapy was 4.2±0.9years; rhGH dose was 0.3±0.07mg/kg/week. Height SDS at baseline was lower in rhGH-treated patients than in controls (-2.00±1.02 versus -0.96±1.11, p<0.001). Baseline height SDS was significantly lower than target height SDS in both groups. Height SDS significantly improved from baseline to final height attainment in rhGH-treated patients, while it slightly decreased in controls (mean SDS variation 0.69±1.05 in rhGH-treated cases versus -0.15±1.2 in controls). Final height SDS was -1.25±1.06 in rhGH-treated cases and -1.06±1.17 in controls (p=0.29). Target adjusted final height SDS was -0.91±1.03 in rhGH-treated cases and -0.61±1.17 in controls (p=0.1). Long-term rhGH therapy is able to reduce the linear growth deceleration of children with CKD, and ultimately to improve their final height, reducing the difference with target height.

Validation of the G.LAB MD2680 digital automatic blood pressure monitor according to international protocols.

The aim of this study was to validate the G.LAB MD2680 digital automatic blood pressure (BP) monitor according to major international protocols. The device was evaluated against auscultatory sphygmomanometry according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010, the British Hypertension Society (BHS), and the International Organization for Standardization (ISO) 81060-2:2013 protocols. Bland-Altman plots were completed for systolic (SBP) and diastolic blood pressures (DBP), and the mean differences and SDs between the test device and the reference device were computed for all BP values. The G.LAB MD2680 passed the ESH-IP revision 2010 on 33 participants with a mean device-observer difference of 0.89±4.97 mmHg for SBP and 0.72±4.91 mmHg for DBP, respectively. The device achieved A/A grading for the BHS protocol among 85 participants with a device-observer difference of 0.70±6.35 mmHg for SBP and 0.62±6.41 mmHg for DBP, respectively. Furthermore, it also fulfilled the two criteria of the ISO 81060-2:2013 protocol. The G.LAB MD2680 digital automatic BP monitor fulfilled the accuracy requirements of the ESH-IP revision 2010 and the ISO 81060-2:2013 protocols, and achieved A/A grade of the BHS protocol, and it can be recommended for self-measurement in adults.

Long-term growth and development in 268 bevacizumab (BEV)-treated and 135 control pediatric/adolescent patients (pts): An integrated analysis.

10554 Background: BEV has an established safety profile in adults, but long-term data in children are limited. This analysis examined the effects of BEV on growth/development in pediatric/adolescent pts. Methods: Data (height, weight, body mass index [BMI], bone age data) were pooled (5 trials): NCT00643565 (Ph2/soft tissue sarcoma); NCT01390948 (Ph2/high-grade glioma); NCT00085111 (Ph1/refractory solid tumors); NCT00667342 (Ph2/osteosarcoma); NCT00381797 (Ph2/glioma, medulloblastoma, ependymoma). Pts (&lt;18 yrs old) received ≥1 dose of BEV + chemotherapy (CT) (n=268) or CT alone (n=135). Analyses were exploratory/descriptive. Reference growth data: WHO (&lt;2 yrs); Centres for Disease Control (≥2 yrs). Results: Across the trials, mean number of BEV administrations per pt ranged 5.6–19.9 (dose 5–15mg/kg every 2/3 weeks). Median follow-up time, months (range): BEV+CT, 37.9 (2.4–64.2); CT, 22.9 (2.8–69.2). At baseline, median height, weight, and BMI were close to that of the reference population (mean standard deviation scores [SDS] close to 0). Over 60 months, a slight decline was observed in the mean SDS for height and weight in both arms in this cohort with different tumors/treatments (Table), but remained within normal range of healthy children. Trends were similar for BMI. No delay in growth velocity or bone age in BEV-treated pts vs CT only was observed up to 3 yrs, regardless of age/gender. A subgroup analysis of pts in the growth hormone-dependent development phase was consistent with the overall results. Conclusions: In this analysis, BEV inclusion in the treatment regimen did not have a negative impact on pediatric growth/development beyond that of CT alone. [Table: see text]

Early cortical metabolic rearrangement related to clinical data in idiopathic sudden sensorineural hearing loss

Results in studies concerning cortical changes in idiopathic sudden sensorineural hearing loss (ISSNHL) are not homogeneous, in particular due to the different neuroimaging techniques implemented and the diverse stages of ISSNHL studied. Considering the recent advances in state-of-the-art positron emission tomography (PET) cameras, the aim of this study was to gain more insight into the neuroanatomical differences associated with the earliest stages of unilateral ISSNHL and clinical-perceptual performance changes.After an audiological examination including the mean auditory threshold (mean AT), mean speech discrimination score (mean SDS) and Tinnitus Handicap Inventory (THI), 14 right-handed ISSNHL patients underwent brain [18F]fluorodeoxyglucose (FDG)-PET within 72 h of the onset of symptoms. When compared to an homogeneous group of 35 healthy subjects by means of statistical parametric mapping, a relative increase in FDG uptake was found in the right superior and medial frontal gyrus as well as in the right anterior cingulate cortex in ISSNHL patients. Conversely, the same group showed a significant relative decrease in FDG uptake in the right middle temporal, precentral and postcentral gyrus as well as in the left posterior cingulate cortex, left lingual, superior, middle temporal and middle frontal gyrus and in the left insula. Regression analysis showed a positive correlation between mean THI and glucose consumption in the right anterior cingulate cortex and a positive correlation between mean SDS and glucose consumption in the left precentral gyrus.The relative changes in FDG uptake found in these brain regions and the positive correlation with mean SDS and THI scores in ISSNHL could possibly highlight new aspects of cerebral rearrangement, contributing to further explain changes in those functions that support speech recognition during the sudden impairment of unilateral auditory input.

Determinants of exercise capacity in school-aged esophageal atresia patients.

Data on long-term outcome of exercise capacity in school-aged children with esophageal atresia (EA) are scarce. We evaluated maximal exercise capacity and its relation to lung function. Moreover, we studied other possible determinants of exercise capacity and lung function. Exercise capacity of 63 children with EA born 1999-2007 was evaluated at the age of 8 years with the Bruce-protocol. Dynamic and static lung volumes, bronchodilator response and diffusion capacity were measured. Furthermore, perinatal characteristics, hospital admissions for lower respiratory tract infections (RTIs), RTIs treated with antibiotics in the past year, symptoms of gastroesophageal reflux, weight-for-height, and sports participation were evaluated as other potential determinants. Exercise capacity was significantly below normal: mean (SD) SDS -0.91 (0.97); P < 0.001. All spirometric parameters were significantly below normal with significant reversibility of airflow obstruction in 13.5% of patients. Static lung volumes were significantly decreased (mean (SD) SDS TLChe -1.06 (1.29); P < 0.001). Diffusion capacity corrected for alveolar volume was normal (mean (SD) SDS KCO -0.12 (1.04)). Exercise capacity was positively associated with total lung capacity and negatively with SDS weight-for-height. Spirometric parameters were negatively associated with congenital cardiac malformation, duration of ventilation, and persistent respiratory morbidity. Eight-year-old children with EA had reduced exercise capacity which was only associated with the reduction in TLChe and higher SDS weight-for-height. We speculate that diminished physical activity with recurrent respiratory tract infections may also play a role in reduced exercise capacity. This should be subject to further research to optimize appropriate intervention.